To investigate the effects of genetic and environmental factors, and their interactions, on respiratory health in adults we have established several high-quality population resources. We have been working with the extramurally funded cohort, the Atherosclerosis Risk in Communities (ARIC) study to examine both genetic and environmental factors in adult respiratory health. The ARIC study is a cohort of 16,000 adults assembled from 1987-1989 in four US communities. ARIC has a wealth of detailed cardiovascular and respiratory phenotypes. We have used the genome wide association genotyping in ARIC to look for novel genes associated with pulmonary function and chronic obstructive pulmonary disease (COPD). In 2009, we formed a pulmonary function analysis group within the CHARGE consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology) which includes several other cohorts with genome wide association genotyping and pulmonary function data (Hancock et al. Nat Genet 2009). In our CHARGE meta-analysis, we identified eight novel loci related to pulmonary function. All but one have now been replicated by other groups. We subsequently developed a collaborated with a European consortium (SpiroMeta) to expand our work. We have published joint consortium papers on pulmonary function (Soler Artigas et al. Nat Genet 2011) and COPD (Wilk et al. AJRCCM 2012). We have submitted a paper on genome wide interaction with smoking in relation to pulmonary function and are working on analysis of longitudinal change in pulmonary function and additional analyses. Over the past several years, I have been collaborating with Jane Hoppin and others at NIEHS and NCI to examine agricultural factors in relation to asthma and COPD phenotypes in the Agricultural Health Study (AHS), a large cohort of farmers and their spouses in Iowa and North Carolina. To date, we have had a number of interesting findings based on very simple questionnaire outcomes. We continued to expand these observations in new papers this year. To follow-up on these observations, we are doing a new study which is described in a separate annual report - ES102385-01. Another population is the NIEHS Sister Study. This NIEHS cohort has enrolled 50,000 sisters of women with breast cancer. I have added nonmalignant respiratory disease questions to the questionnaire with the aim of examining gene-environment interaction in relation to respiratory disease in this cohort as it matures. The cohort is being followed up annually. In collaboration with investigators at the EPA-UNC Human Exposure Facility, I have established a study to follow-up on recent experimental work showing that obese mice have greater respiratory response to ozone than lean mice. This work also follows up our recent finding that subjects with higher BMI have greater drop in pulmonary function (FEV1) in response to acute ozone exposure(Bennett et al., Inhalation Toxicology, 2007). We have established an experimental study where we expose centrally obese and lean women to ozone and measure spirometry, air resistance, airway hyperresonsiveness and inflammatory responses to the exposure. We have completed enrollment for this study.